NEJM: This rare disease that died before the age of 10 was repaired by lentiviral gene therapy

Written | Edited by Wang Cong | Typeset by Wang Duoyu | Shuichengwen Hurler syndrome, also called mucopolysaccharidosis type IH (MPS-IH), is a rare autosomal recessive genetic disease
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Due to genetic mutations, α-L-iduronidase (IDUA) is lacking, which in turn causes mucopolysaccharides to decompose and accumulate in the body
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It is the most common and severe type of mucopolysaccharidosis
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Children often have a period of normal development (a few weeks to 1 year) after birth, and then gradually develop physical and intellectual development disorders
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Most of them have significant symptoms at 16-18 months and usually die before the age of 10
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Allogeneic hematopoietic stem cell transplantation is the standard treatment for Hurler syndrome.
However, this treatment can only be partially cured and is accompanied by complications.
The transplant-related mortality is relatively high
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Recently, the New England Journal of Medicine (NEJM) published a clinical research paper entitled: Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome
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Eight children with Hurler syndrome received autologous hematopoietic stem or progenitor cell therapy.
These cells were transduced in vitro with a lentivirus encoding α-L-iduronidase.
After treatment, the peripheral tissues and central The metabolism of the nervous system has been extensively corrected
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These 8 children who received treatment lacked suitable donors for allogeneic hematopoietic stem cell transplantation, and their developmental quotient or IQ test scores were higher than 70, which means that none of them had moderate or severe cognitive impairment.

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Under myeloablative conditions, children who were 1.
9 ± 0.
5 years old at the time of these treatments received autologous hematopoietic stem and progenitor cell (HSPC) transplants
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These cells were derived from the patients themselves and were transduced in vitro with a lentivirus encoding α-L-iduronidase (IDUA), allowing these cells to express α-L-iduronidase ( IDUA)
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The planned duration of this clinical trial is 5 years, and this paper is an interim report with a median follow-up time of 2.
1 years
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The interim report shows that the safety of the treatment is similar to other known autologous hematopoietic stem cell transplants
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All patients showed rapid and continuous implantation of genetic correction cells, and produced active α-L-iduronidase (IDUA) within one month, and it continued
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The level of mucopolysaccharide in urine dropped sharply.
At 12 months after treatment, 4 out of 5 evaluable children reached normal levels
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The presence of α-L-iduronidase (IDUA) could not be detected before in the cerebrospinal fluid of children, but it can be detected after treatment, and it is related to the local clearance of mucopolysaccharides
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More importantly, the treated children showed stable cognitive ability, stable motor skills corresponding to continuous motor development, improvement or stabilization of magnetic resonance imaging of the brain and spine, reduced joint stiffness, and compliance with World Health Organization growth Chart of normal growth and development
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These results show that after gene therapy of autologous hematopoietic stem cells or progenitor cells in children with Hurler syndrome, the metabolism of the peripheral tissues and central nervous system of the children has been extensively corrected, which also supports the clinical application of this therapy.
Further advancement in China
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Link to the paper: https:// is open for reprinting, welcome to forward to Moments and WeChat groups